Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVCMZXB)

• DOT Name: Glutathione S-transferase LANCL1 (LANCL1)
• Synonyms: EC 2.5.1.18; 40 kDa erythrocyte membrane protein; p40; LanC-like protein 1
• Gene Name: LANCL1
• UniProt ID: LANC1_HUMAN
• PDB ID: 3E6U; 3E73; 8CZK; 8CZL; 8D0V; 8D19
• EC Number: 2.5.1.18
• Pfam ID: PF05147
• Sequence:
  MAQRAFPNPYADYNKSLAEGYFDAAGRLTPEFSQRLTNKIRELLQQMERGLKSADPRDGT
  GYTGWAGIAVLYLHLYDVFGDPAYLQLAHGYVKQSLNCLTKRSITFLCGDAGPLAVAAVL
  YHKMNNEKQAEDCITRLIHLNKIDPHAPNEMLYGRIGYIYALLFVNKNFGVEKIPQSHIQ
  QICETILTSGENLARKRNFTAKSPLMYEWYQEYYVGAAHGLAGIYYYLMQPSLQVSQGKL
  HSLVKPSVDYVCQLKFPSGNYPPCIGDNRDLLVHWCHGAPGVIYMLIQAYKVFREEKYLC
  DAYQCADVIWQYGLLKKGYGLCHGSAGNAYAFLTLYNLTQDMKYLYRACKFAEWCLEYGE
  HGCRTPDTPFSLFEGMAGTIYFLADLLVPTKARFPAFEL
• Function: Functions as a glutathione transferase. Catalyzes conjugation of the glutathione (GSH) to artificial substrates 1-chloro-2,4-dinitrobenzene (CDNB) and p-nitrophenyl acetate. Mitigates neuronal oxidative stress during normal postnatal development and in response to oxidative stresses probably through GSH antioxidant defense mechanism. May play a role in EPS8 signaling. Binds glutathione.
• Tissue Specificity: Detected in erythrocytes, brain, kidney, testis, ovary, heart, lung, placenta and spleen (at protein level). Ubiquitous. Strongly expressed in brain, spinal cord, pituitary gland, kidney, heart, skeletal muscle, pancreas, ovary and testis.
• KEGG Pathway:
  Glutathione metabolism (hsa00480)
  Metabolic pathways (hsa01100)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Glutathione S-transferase LANCL1 (LANCL1) affects the response to substance of Cisplatin.	[9]
Etoposide	DMNH3PG	Approved	Glutathione S-transferase LANCL1 (LANCL1) affects the response to substance of Etoposide.	[9]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Glutathione S-transferase LANCL1 (LANCL1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glutathione S-transferase LANCL1 (LANCL1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Glutathione S-transferase LANCL1 (LANCL1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Glutathione S-transferase LANCL1 (LANCL1).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glutathione S-transferase LANCL1 (LANCL1).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Glutathione S-transferase LANCL1 (LANCL1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Glutathione S-transferase LANCL1 (LANCL1).	[7]
Taurine	DMVW7N3	Investigative	Taurine increases the expression of Glutathione S-transferase LANCL1 (LANCL1).	[8]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [7] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [8] Taurine-responsive genes related to signal transduction as identified by cDNA microarray analyses of HepG2 cells. J Med Food. 2006 Spring;9(1):33-41. doi: 10.1089/jmf.2006.9.33.
• [9] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.